By Frances Bishopp
Interneuron Pharmaceuticals Inc. reported Monday neuropsychological test findings among patients recovering from ischemic stroke have demonstrated a significant improvement in the cognitive function of those patients who received citicoline, Interneuron's drug being developed for stroke.
These findings follow last year's Phase III clinical trial results with these patients, who also exhibited significantly improved neurologic function, as assessed by the Barthel Index (a standard of measuring neurologic function) at 12 weeks following stroke, William Boni, vice president of corporate communications, told BioWorld Today.
"In the area of stroke you look for neurologic function improvement; this marks one of the first times that learning and memorization skills have been prospectively defined and analyzed in as systematic and extensive a fashion," Boni said. "This was another endpoint in the trial, but clearly secondary."
The findings of the Phase III trial demonstrated that patients who were given 500 milligrams of citicoline within 24 hours following the onset of stroke symptoms and continuously for six weeks thereafter, scored statistically significantly higher on a battery of tests measuring learning ability and memorization skills than did patients who received placebo.
Analyst David Crossen, of Montgomery Securities, of San Francisco, told BioWorld Today. "The functional improvement as shown by a variety of scores is really quite impressive. The proportion of patients who showed complete functional or near complete functional improvement or recovery was significantly increased with the drug in that 24-hour window in which it is given."
"This additional piece [of information] actually broadens the concept of what an ideal stroke drug should do. Not only do you get functional improvement, but the suggestion is that that will be accompanied by improvements in cognitive or thinking performance," Crossen said.
"There has been no stroke drug ever that has shown this dramatic effect with this wide a window," Crossen said. "This drug is a real breakthrough and has the potential to be a million-dollar product."
Boni said Interneuron, of Lexington, Mass., currently has an ongoing Phase III trial similar to the one completed last year (neurologic function as assessed by the Barthel Index) that is expected to be completed by late summer. At this point, Boni said, no more trials are planned for citicoline with cognitive function as the endpoint, given the fact that the FDA's focus is on neurologic findings.
Boni said if the ongoing trial is positive, Interneuron hopes to file a new drug application by the end of 1997.
Citicoline, a small molecule, is believed to have multiple mechanisms of action: it limits the extent of the infarct, or tissue damage caused by interrupted blood flow, by preventing the accumulation of toxic free fatty acids; it promotes recovery of brain function by providing two components, cytidine and choline, required in the formation of nerve cell membranes and it promotes the synthesis of acetylcholine, a neurotransmitter associated with cognitive function.
The neurocognitive tests administered in this trial included the Folstein Mini-Mental State Examination, the Hopkins Verbal Learning Test, Span Tests and Trailmaking Tests.
Interneuron's other products include Redux (dexfenfluramine), which was approved for weight loss last April and bucindolol, a third-generation beta blocker being developed by Intercardia Inc., of Research Triangle Park, N.C., for the treatment of heart failure. Interneuron owns 60 percent of Intercardia.
Besides Intercardia, Interneuron's subsidiaries include: Progenitor Inc., focused on gene discovery through developmental biology, Transcell Technologies Inc., which specializes in carbohydrate-based drug discovery and drug transport and InterNutria Inc., focused on dietary supplement products.
Interneuron's most recent public offering (June 1996) resulted in net proceeds of approximately $109 million.
Interneuron was founded in 1988 and went public in 1990. The company has cash on hand of approximately $168 million. Interneuron's stock (NASDAQ:IPIC) closed down $1.125 Monday to $30.625. *